Performance of Kidney Injury Molecule-1 and Liver Fatty Acid-Binding Protein and Combined Biomarkers of AKI after Cardiac Surgery

Parikh, Chirag R.; Thiessen-Philbrook, Heather; Garg, Amit X.; Kadiyala, Deepak; Shlipak, Michael G.; Koyner, Jay L.; Edelstein, Charles L.; Devarajan, Prasad; Patel, Uptal D.; Zappitelli, Michael; Krawczeski, Catherine D.; Passik, Cary S.; Coca, Steven G.

doi:10.2215/cjn.10971012

Cited by 205 publications

(213 citation statements)

References 35 publications

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“…Before surgery, for example, we had already observed significant differences in IL-6 among patients who went on to develop both AKI and severe AKI. Our findings build on our previous work that has provided both diagnostic and prognostic information for clinical prediction models [26][27][28][29][30][31][32][33][34] and demonstrates that these cytokines may serve as prognostic biomarkers for perioperative outcomes.…”

Section: Discussionsupporting

confidence: 81%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

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176

119

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Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a $50% or $0.3-mg/dl increase in serum creatinine from baseline. Pre-and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. AKI is a common complication of cardiac surgery, leading to increased morbidity and mortality. 1 Current paradigms of diagnosis and treatment are based on serum creatinine and are thus insensitive. These limitations have spurred the search for novel proteins that are involved in the process of kidney injury. 2,3 While AKI is traditionally recognized and diagnosed by renal functional impairment and structural damage, it is also an inflammatory condition. Understanding and measuring the processes of inflammation in AKI may provide unique tools for its assessment and prediction.To this end, we developed an ancillary study to our large, multicenter cohort study of adult patients

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Section: Discussionsupporting

confidence: 81%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

Self Cite

176

119

View full text Add to dashboard Cite

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“…Therefore, it has been proposed that KIM-1 could play a role in renal recovery and tubular regeneration after AKI (27). Such a role seems congruent with the late timing of peak changes (2-3 days after injury) in urine KIM-1 concentration during AKI (4,26). Pharmacologic interventions that enhance the effect of KIM-1 could potentially benefit patients by facilitating effective clearance of debris from the injured tubules.…”

Section: Kim-1mentioning

confidence: 97%

“…Unfortunately, the clinical use of novel AKI biomarkers is unclear, because large, prospective, multicenter trials, such as the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) (n=1530) study failed to show troponinlike diagnostic performance (3)(4)(5)(6). The recent SAPPHIRE study (n=728) could represent an important moment in AKI biomarker research (7).…”

Section: The Search For a Kidney Troponinmentioning

confidence: 99%

Biomarkers of AKI

Alge

Arthur

2015

Clinical Journal of the American Society of Nephrology

268

188

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AKI is a common clinical condition associated with a number of adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and has led to the discovery of numerous novel biomarkers. However, in addition to facilitating more timely intervention, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Furthermore, AKI biomarkers could also function as molecular phenotyping tools that could be used to direct clinical intervention. This review highlights the major studies that have characterized the diagnostic and prognostic predictive power of these biomarkers. The mechanistic relevance of neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, IL-18, livertype fatty acid-binding protein, angiotensinogen, tissue inhibitor of metalloproteinase-2, and IGF-binding protein 7 to the pathogenesis and pathobiology of AKI is discussed, putting these biomarkers in the context of the progressive phases of AKI. A biomarker-integrated model of AKI is proposed, which summarizes the current state of knowledge regarding the roles of these biomarkers and the molecular and cellular biology of AKI.

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“…Consequently, research in the last decade has focussed on the discovery and validation of more specific and sensitive markers of tubular damage/functional impairment. The most advanced biomarkers promise to identify patients at risk of AKI, diagnose AKI earlier than conventional tests and prognosticate risk of progression, including need for (RRT) renal replacement therapy [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The hope is that, with such an approach and more timely and relevant interventions, the outcome of patients with AKI can be improved.…”

mentioning

confidence: 99%